Is Platelet Heterogeneity Due to Ageing or Thrombopoiesis?

  • M. A. Packham
  • M. L. Rand


The question is not just “Is platelet heterogeneity due to ageing or thrombopoiesis?” The question also implies an attempt to understand what happens to platelets as they circulate under normal and abnormal conditions, and why and how they are eventually removed from the circulation. What changes occur in platelets when they interact with an injury site on a vessel wall, or encounter an aggregating agent in the circulation? The petechial haemorrhages that are characteristic of thrombocytopenia indicate that platelets are necessary to maintain the integrity of the endothelium. How do they support the endothelium and are they altered in doing so? No attempt will be made in this review to answer all these questions, but they are posed to illustrate that it is not unreasonable to suggest that platelets may be changed because of their encounters in the circulation.


Human Platelet Specific Radioactivity Buoyant Density Rabbit Platelet Platelet Survival 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amorosi E, Garg SK, Karpatkin S (1971) Heterogeneity of human platelets. IV. Identification of a young platelet population with [75Se]selenomethionine. Br J Haematol 21:227–232CrossRefGoogle Scholar
  2. Ardlie NG, Packham MA, Mustard JF (1970) Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. Br J Haematol 19:7–17PubMedCrossRefGoogle Scholar
  3. Bolin RB, Medina F, Cheney BA (1981) Glycoprotein changes in fresh vs. room temperature-stored platelets and their buoyant density cohorts. J Lab Clin Med 98:500–510PubMedGoogle Scholar
  4. Boneu B, Boneu A, Raisson C, Guiraud R, Biermé R (1973) Kinetics of platelet “populations” in the stationary state. Thromb Res 3:605–611CrossRefGoogle Scholar
  5. Boneu B, Sié P, Caranobe C, Nouvel C, Bienne R (1980) Malondialdehyde (MDA) re-appearance in human platelet density subpopulations after a single intake of aspirin. Thromb Res 19:609–620PubMedCrossRefGoogle Scholar
  6. Boneu B, Sié P, Eche N, Caranobe C, Hugo B, Nouvel C (1983) Platelet density analysis: a tool for the detection of acquired storage pool disease in man. Br J Haematol 55:523–532PubMedCrossRefGoogle Scholar
  7. Busch C, Olson PS (1973) Density distribution of 51Cr-labelled platelets within the circulating dog platelet population. Thromb Res 3:1–11CrossRefGoogle Scholar
  8. Chamberlain KG, Chiu E, Penington DG (1984) Relationship of platelet density to ageing. Cohort studies using mono-amine oxidase activity. Pathology 16:355Google Scholar
  9. Chamberlain KG, Penington DG (1988) Monoamine oxidase and other mitochondrial enzymes in density subpopulations of human platelets. Thromb Haemost 59:29–33PubMedGoogle Scholar
  10. Charmatz A, Karpatkin S (1974) Heterogeneity of rabbit platelets. I. Employment of an albumin density gradient for separation of a young platelet population identified with Se75-selenomethionine. Thromb Diath Haemorrh 31:485–492PubMedGoogle Scholar
  11. Cieslar P, Greenberg JP, Rand ML, Packham MA, Kinlough-Rathbone RL, Mustard, JF (1979) Separation of thrombin-treated platelets from normal platelets by density-gradient centrifugation. Blood 53:867–874PubMedGoogle Scholar
  12. Corash L, Mok Y (1984) Platelet heterogeneity: density distribution of alpha granule and lysosomal constituents in native and thrombin stimulated platelet density cohorts. Blood 64:245aGoogle Scholar
  13. Corash L, Shafer B (1982) Use of asplenic rabbits to demonstrate that platelet age and density are related. Blood 60:166–171PubMedGoogle Scholar
  14. Corash L, Tan H, Gralnick HR, Shafer B (1977) Heterogeneity of human whole blood platelet subpopulations. I. Relationship between buoyant density, cell volume, and ultrastructure. Blood 49:71–87PubMedGoogle Scholar
  15. Corash L, Shafer B, Perlow M (1978) Heterogeneity of human whole blood platelet subpopulations. II. Use of a subhuman primate model to analyze the relationship between density and platelet age. Blood 52:726–734PubMedGoogle Scholar
  16. Corash L, Costa JL, Shafer B, Donlon JA, Murphy D (1984) Heterogeneity of human whole blood platelet subpopulations. III. Density-dependent differences in subcellular constituents. Blood 64:185–193PubMedGoogle Scholar
  17. Duyvené de Wit LJ, Badenhorst PN, Heyns AduP (1987) Ultrastructural morphometric observations on serial sectioned human blood platelet subpopulations. Eur J Cell Biol 43:408–411PubMedGoogle Scholar
  18. Evans RM, Packham MA, Rand ML et al. (1985) Platelet buoyant density: similar results by centrifugation on discontinuous Stractan and continuous Percoll gradients. Thromb Haemost 54:243Google Scholar
  19. Friedhoff AJ, Miller JC, Karpatkin S (1978) Heterogeneity of human platelets. VII. Platelet monoamine oxidase activity in normals and patients with autoimmune thrombocytopenic purpura and reactive thrombocytosis: its relationship to platelet protein density. Blood 51:317–323PubMedGoogle Scholar
  20. Gear ARL (1981) Preaggregation reactions of platelets. Blood 58:477–490PubMedGoogle Scholar
  21. Greenberg J, Packham MA, Cazenave J-P, Reimers HJ, Mustard JF (1975) Effects on platelet function of removal of platelet sialic acid by neuraminidase. Lab Invest 32:476–484PubMedGoogle Scholar
  22. Greenberg JP, Packham MA, Guccione MA, Rand ML, Reimers H-J, Mustard JF (1979) Survival of rabbit platelets treated in vitro with chymotrypsin, plasmin, trypsin, or neuraminidase. Blood 53:916–927PubMedGoogle Scholar
  23. Guccione MA, Kinlough-Rathbone RL, Packham MA et al. (1985) Effects of plasmin on rabbit platelets. Thromb Haemost 53:8–14PubMedGoogle Scholar
  24. Harfenist EJ, Wrana JL, Packham MA, Mustard JF (1985) Measurement of fibrinogen concentrations in suspensions of washed rabbit and human platelets by radioimmunoassays. Thromb Haemost 53:110–115PubMedGoogle Scholar
  25. Hirsh J, Glynn MF, Mustard JF (1968) The effect of platelet age on platelet adherence to collagen. J Clin Invest 47:466–473PubMedCrossRefGoogle Scholar
  26. Illes I, Pfueller SL, Hussein S, Chesterman CN, Martin JF (1987) Platelets in idiopathic thrombocytopenic purpura are increased in size but are of normal density. Br J Haematol 67:173–176PubMedCrossRefGoogle Scholar
  27. Jung SM, Tanoue K, Yamazaki H (1985) The electrophoretic mobility heterogeneity of human platelet subpopulations of different buoyant densities. Thromb Haemost 53:188–194PubMedGoogle Scholar
  28. Karpatkin S (1969) Heterogeneity of human platelets. II. Functional evidence suggestive of young and old platelets. J Clin Invest 48:1083–1087PubMedCrossRefGoogle Scholar
  29. Karpatkin S (1978) Heterogeneity of rabbit platelets. VI. Further resolution of changes in platelet density, volume and radioactivity following cohort labelling with 75Se-selenomethionine. Br J Haematol 39:459–469PubMedCrossRefGoogle Scholar
  30. Karpatkin S, Charmatz A (1969) Heterogeneity of human platelets. I. Metabolic and kinetic evidence suggestive of young and old platelets. J Clin Invest 48:1073–1082PubMedCrossRefGoogle Scholar
  31. Karpatkin S, Strick N (1972) Heterogeneity of human platelets. V. Differences in glycolytic and related enzymes with possible relation to platelet age. J Clin Invest 51:1235–1243PubMedCrossRefGoogle Scholar
  32. Kelton JG, Denomme G (1982) The quantitation of platelet-associated IgG on cohorts of platelets separated from healthy individuals by buoyant density centrifugation. Blood 60:136–139PubMedGoogle Scholar
  33. Khansari N, Fudenberg HH (1983) Immune elimination of aging platelets by autologous monocytes: Role of membrane-specific autoantibody. Eur J Immunol 13:990–994PubMedCrossRefGoogle Scholar
  34. Kinlough-Rathbone RL, Packham MA, Mustard JF (1983) Vessel injury, platelet adherence, and platelet survival. Arteriosclerosis 3:529–546PubMedCrossRefGoogle Scholar
  35. Leone G, Agostini A, Decrescenzo A, Bizzi B (1979) Platelet heterogeneity. Relationship between buoyant density, size, lipid peroxidation and platelet age. Scand J Haematol 23:204–210PubMedCrossRefGoogle Scholar
  36. Martin JF, Penington DG (1983) The relationship between the age and density of circulating 51Cr-labelled platelets in the sub-human primate. Thromb Res 30:157–164PubMedCrossRefGoogle Scholar
  37. Martin JF, Shaw T, Jakubowski J, Penington DG, Martin TJ (1981) Production of thromboxane B2 by platelets is related to their density. Thromb Haemost 46:198Google Scholar
  38. Martin JF, Shaw T, Heggie J, Penington DG (1983) Measurement of the density of human platelets and its relationship to volume. Br J Haematol 54:337–352PubMedCrossRefGoogle Scholar
  39. McDonald JWD, Ali M (1983) Recovery of cyclooxygenase activity after aspirin in populations of platelets separated on Stractan density gradients. Prostaglandins Leukotrienes Med 12:245–252CrossRefGoogle Scholar
  40. Mezzano D, Aster RH (1987) Survival of platelet density subpopulations. Br J Haematol 65:505CrossRefGoogle Scholar
  41. Mezzano D, Hwang K-L, Catalano P, Aster RH (1981) Evidence that platelet buoyant density, but not size, correlates with platelet age in man. Am J Hematol 11:61–76PubMedCrossRefGoogle Scholar
  42. Mezzano D, Aranda E, Foradori A, Rodriguez S, Lira P (1984a) Kinetics of platelet density subpopulations in splenectomized mongrel dogs. Am J Hematol 17:373–382PubMedCrossRefGoogle Scholar
  43. Mezzano D, Aranda E, Rodriguez S, Foradori A, Lira P (1984b) Increase in density and accumulation of serotonin by human aging platelets. Am J Hematol 17:11–21PubMedCrossRefGoogle Scholar
  44. Mezzano D, Aranda E, Foradori A (1986) Comparative study of size, total protein, fibrinogen and 5-HT content of human and canine platelet density subpopulations. Thromb Haemost 56:288–292PubMedGoogle Scholar
  45. Minter FM, Ingram M (1971) Platelet volume : density relationships in normal and acutely bled dogs. Br J Haematol 20:55–68PubMedCrossRefGoogle Scholar
  46. Packham MA, Guccione MA, Kinlough-Rathbone RL, Mustard JF (1980) Platelet sialic acid and platelet survival after aggregation by ADP. Blood 56:876–880PubMedGoogle Scholar
  47. Packham MA, Guccione MA, O’Brien KM (1985a) Duration of the effect of aspirin on the synthesis of thromboxane by density subpopulations of rabbit platelets stimulated with thrombin. Blood 66:287–290PubMedGoogle Scholar
  48. Packham MA, Perry DW, Kinlough-Rathbone RL et al. (1985b) Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP. Blood 65:564–570PubMedGoogle Scholar
  49. Packham MA, Kinlough-Rathbone RL, Mustard JF (1987) Thromboxane A2 causes feedback amplification involving extensive thromboxane A2 formation upon close contact of human platelets in media with a low concentration of ionized calcium. Blood 70:647–651PubMedGoogle Scholar
  50. Parker RI, Shafer BC, Gralnick HR (1987) Platelet density-dependent partitioning of platelet-von Willebrand factor between alpha granule and non-alpha granule pools. Thromb Haemost 58:911–914PubMedGoogle Scholar
  51. Penington DG (1984) Heterogeneity of platelets. Br J Haematol 56:351–352CrossRefGoogle Scholar
  52. Penington DG, Lee NLY, Roxburgh AE, McGready JR (1976a) Platelet density and size: The interpretation of heterogeneity. Br J Haematol 34:365–376PubMedCrossRefGoogle Scholar
  53. Penington DG, Streatfield K, Roxburgh AE (1976b) Megakaryocytes and the heterogeneity of circulating platelets. Br J Haematol 34:639–653PubMedCrossRefGoogle Scholar
  54. Pereira J, Cretney C, Aster RH (1988) Variation of class I HLA antigen expression among platelet density cohorts: a possible index of platelet age? Blood 71:516–519PubMedGoogle Scholar
  55. Pfueller SL, Chesterman C, Illes I, Hussein S, Martin JF (1986) Relationship of platelet-associated immunoglobulin G and platelet protein to platelet size and density in normal individuals and patients with thrombocytopenia. J Lab Clin Med 107:299–305PubMedGoogle Scholar
  56. Rand ML (1983) Studies of changes in rabbit platelets as they age in vivo. PhD thesis, University of Toronto, Toronto, CanadaGoogle Scholar
  57. Rand ML, Greenberg JP, Packham MA, Mustard JF (1981) Density subpopulations of rabbit platelets: size, protein, and sialic acid content, and specific radioactivity changes following labeling with 35S-sulfate in vivo. Blood 57:741–746PubMedGoogle Scholar
  58. Rand ML, Packham MA, Guccione MA, Mustard JF (1983a) Glycoproteins of rabbit platelets: Loss from granules during aging in vivo or as a result of the release reaction in vitro. Thromb Haemost 50:188Google Scholar
  59. Rand ML, Packham MA, Mustard JF (1983b) Survival of density subpopulations of rabbit platelets: Use of 51Cr- or 111In-labeled platelets to measure survival of least dense and most dense platelets concurrently. Blood 61:362–367PubMedGoogle Scholar
  60. Reimers HJ, Packham MA, Kinlough-Rathbone RL, Mustard JF (1973) Effect of repeated treatment of rabbit platelets with low concentrations of thrombin on their function, metabolism and survival. Br J Haematol 25:675–689PubMedCrossRefGoogle Scholar
  61. Reimers HJ, Kinlough-Rathbone RL, Cazenave J-P et al. (1976) In vitro and in vivo functions of thrombin-treated platelets. Thromb Haemost 35:151–166PubMedGoogle Scholar
  62. Savage B, McFadden PR, Hanson SR, Harker LA (1986) The relation of platelet density to platelet age: survival of low- and high-density 111Indium-labeled platelets in baboons. Blood 68:386–393PubMedGoogle Scholar
  63. Somers DA (1984) The relation among vessel injury, thombus formation and platelet survival. PhD thesis, McMaster University, Hamilton, Ontario, CanadaGoogle Scholar
  64. Somers DA, Winocour PD, Kinlough-Rathbone RL, Mustard JF (1983) Relation among platelet survival, vessel injury, thrombosis and platelet density. Fed Proc 42:1027Google Scholar
  65. van Oost BA, van Hien-Hagg IH, Veldhuyzen BFE, Timmermans APM, Sixma JJ (1982) Determination of the density distribution of human platelets: methodological aspects and comparison with other tests of platelet activation. Thromb Haemost 47:239–243PubMedGoogle Scholar
  66. van Oost B, van Hien-Hagg IH, Timmermans APM, Sixma JJ (1983) The effect of thrombin on the density distribution of blood platelets: detection of activated platelets in the circulation. Blood 62:433–438PubMedGoogle Scholar
  67. van Oost B, Timmermans APM, Sixma JJ (1984) Evidence that platelet density depends on the oc- granule content in platelets. Blood 63:482–485PubMedGoogle Scholar
  68. Vicie WJ, Weiss HI (1983) Evidence that platelet α-granules are a major determinant of platelet density: studies in storage pool deficiency. Thromb Haemost 50:878–880Google Scholar
  69. Watson HHK, Ludlam CA (1986) Survival of 111-indium platelet subpopulations of varying density in normal and post splenectomized subjects. Br J Haematol 62:117–124PubMedCrossRefGoogle Scholar
  70. Winocour PD, Kinlough-Rathbone RL, Perry DW, Rand ML, Packham MA, Mustard JF (1983) Changes in the properties of platelets from rats with experimentally induced shortened platelet survival. J Lab Clin Med 101:175–182PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 1990

Authors and Affiliations

  • M. A. Packham
  • M. L. Rand

There are no affiliations available

Personalised recommendations